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LIVER, PANCREAS, AND BILIARY TRACT: CLINICAL REVIEW The Role of Antibiotic Prophylaxis in the Treatment Paul Georg Lankisch, MD, FRCP, FACG and Markus M. Lerch, MD, FRCP, FACG anaerobic bacteria, fungi).2 A positive Gram staining has been Abstract: Acute pancreatitis is an inflammatory disorder, but it is found to be a reliable early indicator of pancreatic infection. In not generally caused by infectious agents. Yet, in tertiary referral one retrospective study, negative Gram staining was followed hospitals, the majority of patients who die of necrotizing pancreatitis by a negative culture. In almost all cases where here was do so as a consequence of infectious complications. These generally a positive culture, the Gram staining also revealed organisms.3 develop late (2–4 weeks) in the disease process. This finding Gram staining is essential, as the results of bacteriologic prompted the hypothesis that infectious pancreatitis complications, cultures may not be available for several days. The compli- such as an abscess or an infected necrosis which can lead to death, cation rate for fine needle aspiration is low.3,4 Rarely, bleeding can be reduced by treating patients who suffer, at least initially, from or an exacerbation of acute pancreatitis will occur.5,6 Although a sterile inflammatory disorder, with broad-spectrum antibiotics. Here six published guidelines on the diagnosis and treatment of we review the experimental foundations of this hypothesis, as well as acute pancreatitis recommend fine needle aspiration for de- the difficulties that were encountered when clinical trials were tecting infected pancreatic necrosis,7–12 it is not mentioned in undertaken to confirm it. At present, there is still a case for treating two guidelines13,14 and the procedure is only performed in necrotizing pancreatitis patients with broad-spectrum antibiotics a minority of centers. In an assessment of the compliance with (specifically carbapenems), but the extent of the beneficial effect and guidelines in Germany, for example, only one third of senior the number of patients expected to profit from this approach should gastroenterologists said that they used the procedure.15,16 Apparently, the majority of respondents diagnose infected pan-creatic necrosis on the basis of unresolved organ failure, per- Key Words: acute pancreatitis, pancreatic necrosis, antibiotic Infected pancreatic necrosis is still assumed to indicate that surgical debridement is necessary. However, during recentyears, several studies have reported that conservative treat- ment such as nonsurgical drainage was successful in some wing to a series of studies initiated by the Ulm group, it is patients.17–19 Criteria to determine whether a patient with known that infection of pancreatic necrosis is a major and infected pancreatic necrosis will benefit from surgical or life-threatening complication of acute necrotizing pancreati- conservative treatment are currently not available.
tis.1 The gold standard for the differentiation between in- Under these conditions, it would be helpful to prevent terstitial pancreatitis (about 80% of the cases) and necrotizing infection of pancreatic necrosis in the first place. The question pancreatitis (about 20% of the cases) remains contrast- whether antibiotics can serve this purpose and can thus enhanced computed tomography (CT). However, this imaging improve patient survival is being controversially discussed.
procedure is not always a helpful tool for diagnosing infection.
Here we review the studies that have investigated Only when air inclusions in or around the necrotic area are whether and which antibiotics penetrate sufficiently well identified on CT is infected necrosis suspected. Otherwise, into pancreatic necrosis and whether prophylactic antibiotic there is no specific feature on contrast-enhanced CT that is treatment of patients with acute pancreatitis is of clinical able to distinguish between infected or sterile necrosis. The gold standard for the detection of infected pancreatic necrosisis ultrasound-guided or CT-guided percutaneous aspiration ofsuspected pancreatic fluid collections with bacteriologic sam- pling. Fluid obtained by this procedure should be processed immediately for Gram staining and culture (aerobic and At present, there are around 13 studies on the pene- tration of antibiotics in the human pancreas, and their resultsdiffer considerably (Table 1).20–32 In most studies, a parenteral Received for publication August 2, 2005; accepted September 1, 2005.
route of administration for the antibiotic was used, which From the Department of General Internal Medicine, Center of Medicine, Municipal Clinic of Lu¨neburg, Lu¨neburg, and the Department of seems appropriate for a patient with acute pancreatitis. Eight Gastroenterology, Endocrinology and Nutrition, Ernst-Moritz-Arndt studies measured the presence and concentration of the anti- University of Greifswald, Greifswald, Germany.
biotic in pancreatic secretion, obtained either on endoscopic Reprints: Paul Georg Lankisch, MD, Klinik fu¨r Allgemeine Innere Medizin, retrograde cholangiopancreatography (ERCP) or after stimu- Sta¨dtisches Klinikum Lueneburg, Boegelstrasse 1, D-21339 Lueneburg, lation via a pancreatic fistula.20–26,32 In one study, the content Germany (e-mail: [email protected]).
Copyright Ó 2006 by Lippincott Williams & Wilkins of pseudocysts was used to test the penetration of the J Clin Gastroenterol  Volume 40, Number 2, February 2006 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Clin Gastroenterol  Volume 40, Number 2, February 2006 TABLE 1. Penetrability of Antibiotics Into Human Pancreatic Juice (Obtained During ERCP or Via a Pancreatic Fistula) and Tissue +, antibiotic detected in sufficiently bactericidal concentrations; 2, antibiotic not detected or in insufficient bactericidal concentrations; AP, acute pancreatitis; CP, chronic pancreatitis; PCA, pancreatic carcinoma; PS, pseudocyst.
antibiotic. In the remaining studies, antibiotic concentrations Gregg et al24 investigated cephalothin and cefoxitin and failed were measured in pancreatic tissue.31 Tissue samples were to detect them in pure pancreatic juice obtained from obtained from patients with different pancreatic diseases and patients with acute relapsing or chronic pancreatitis or in different degrees of inflammation (acute pancreatitis, chronic pancreatitis, pancreatic carcinoma). Human studies29 have Pederzoli et al found sufficiently high and bactericidal con- shown that the antibiotic concentration depends on the degree centrations of mezlocillin,20 ciprofloxacin,26 and ofloxacin of inflammation, with higher levels in acute pancreatitis compared with controls. The following results were reported Brattstro¨m et al23 reported sufficient bactericidal concen- trations of clindamycin but not of cefoxitin or piper- Roberts and Williams21 failed to detect the antibiotic, ampicillin in pancreatic juice obtained by ERCP, which acillin in patients with pancreatic transplants.
was used in initial studies evaluating antibiotics in Koch et al22 tested ampicillin, azlocillin, mezlocillin, cefotiam, gentamicin, doxycycline, chloramphenicol, metronida- Benveniste and Morris32 and Lankisch et al31 reported suffi- zole, and ciprofloxacin and found sufficient bactericidal ciently high and bactericidal concentrations of cefotaxime concentrations of mezlocillin, ciprofloxacin, metronida- in both pancreatic juice and pancreatic pseudocysts.
zole, doxycycline, and chloramphenicol.
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J Clin Gastroenterol  Volume 40, Number 2, February 2006 Antibiotic Prophylaxis in Acute Pancreatitis Bu¨chler et al29 tested mezlocillin, piperacillin, cefotaxime, complete gut decontamination, in a duct hyperstimulation ceftizoxime, netilmicin, tobramycin, ofloxacin, ciproflox- model in the rat. Neither treatment had a positive effect on acin, imipenem, and metronidazole in patients who under- survival. Pancreatic bacterial counts, on the other hand, were went pancreatic surgery for acute or chronic pancreatitis significantly reduced by imipenem, but not by cefotaxime.
or pancreatic carcinoma. Based on the detection of anti- Mitho¨fer et al39 from the same group, used the identical model biotics in pancreatic tissue, three groups of antibiotics to investigate the effect of imipenem and ciprofloxacin but were established: Group A, substances with low tissue increased the antibiotic treatment from 4 to 7 days. The concentrations (aminoglycosidase, netilmicin, tobramy- extended treatment probably accounts for the increased sur- cin) that were below the minimal inhibitory concentra- vival rate in this study. Both antibiotics reduced early and late tions of most bacteria found in pancreatic infection; Group B, antibiotics with pancreatic tissue concen-trations that were sufficient to inhibit some, but not all,bacteria in pancreatic infection (mezclocillin, piperacil- lin, ceftizoxime, cefotaxime); and Group C, substances with high pancreatic tissue levels, as well as high bac-tericidal activity against most of the organisms present in pancreatic infection (ciprofloxacin, ofloxacin, imipe- Three randomized studies were published in the 1970s, in which ampicillin or a placebo was given to less than The Drewelow et al28 and Koch et al30 groups found sufficient 200 patients who had acute pancreatitis, in most cases due to bactericidal concentrations of ceftazidime and ofloxacin alcohol abuse.33–35 Only 1 patient in these studies died and in the pancreatic tissue of patients with a variety of 26 had infectious complications. All studies agreed that am- picillin had no beneficial effect on the clinical course of the Bassi et al27 tested the penetration of imipenem, mezlocillin, disease or on serum pancreatic enzyme elevations.33–35 For gentamicin, amikacin, pefloxacin, and metronidazole in many years, this conclusion led to the erroneous impression cases of pancreatic necrosis. Samples were obtained by that antibiotic prophylaxis was of no benefit in pancreatitis.
fine-needle aspiration or during operation or surgical However, these studies are now recognized as being flawed for drainage. As in the Bu¨chler et al study,29 gentamicin and several reasons. First, ampicillin has a modest spectrum of amikacin were not detected, whereas the others were activity against Gram-negative microorganisms, which are found at sufficiently high bactericidal concentrations.
common in pancreatic infection. Second, ampicillin achievespoor penetration in pancreatic tissue40 and in pancreaticfluid.21 Third, given the low severity of the disease in these studies,33–35 they have insufficient statistical power (Type 2 There are four experimental studies investigating the More recently, six studies, with divergent results, have effect of prophylactic antibiotics for the prevention of pan- been published addressing the question of antibiotic pro- creatic infection in acute pancreatitis (Table 2). Widdison phylaxis in acute necrotizing pancreatitis (Table 3).
et al36 studied the effect of cefotaxime, administered 12 hours In the study by Pederzoli et al,42 74 patients with acute after the induction of acute experimental pancreatitis, using necrotizing pancreatitis, mostly of biliary origin, were a perfusion model in cats. They found that cefotaxime reached selected. The mean Ranson score was 3.7 (mean value) bactericidal levels in pancreatic tissue and juice and and pancreatic necrosis had been proven by CT within significantly prevented pancreatic infection. Araida et al37 72 hours, following the onset of the disease. Patients studied the effect of piperacillin given immediately after the were randomly assigned to two groups: one without induction of acute experimental pancreatitis in the rat (duct antibiotic treatment and one receiving 0.5 g of imipenem model) and found a positive effect both on the infection and every 8 hours for 2 weeks. The incidence of pancreatic sepsis was significantly reduced from 30.3% to 12.2% Foitzik et al38 studied the effect of intravenously and that of nonpancreatic sepsis from 48.5% to 14.6% administered cefotaxime and imipenem plus the effect of (P , 0.01). The rate of multiorgan failure, the need for TABLE 2. Intravenous Antibiotic Treatment in Severe Acute Experimental Pancreatitis (AEP) Duration of treatment: *4 days, †7 days.
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J Clin Gastroenterol  Volume 40, Number 2, February 2006 TABLE 3. Intravenous Antibiotic Prophylaxis in Severe Acute Pancreatitis (AP): Results of Controlled Clinical Studies *Seventy-six patients with necrotizing pancreatitis.
surgical treatment, and the mortality rate were not The Sainio et al study44 has been criticized because of the affected. Antibiotic prophylaxis was especially effective strikingly high number of urinary tract infections and the in patients with mild to moderate necrosis. None of the high rate of S. epidermidis infections.45 S. epidermidis is patients in the antibiotic group with less than 50% not commonly found in infected pancreatic necrosis, and pancreatic necrosis developed septic complications.
the origin of this infection remains unclear.45 Further- This was in contrast to those in the control group.
more, with regard to the choice of cefuroxime, the tissue The study has been criticized for the unequal dis- concentrations may have been suboptimal. Also, the tribution of severe necrosis. Sixteen patients had severe antibiotic regimen had to be changed after a mean of necrosis (.50%), of whom 14 were in the treatment 9.2 days, in 20 of the 30 patients within the treatment group and 2 were in the placebo group. This distribution group. The authors had chosen cefuroxime because of may have precluded a statistically significant effect on the high number of S. aureus infections in their intensive the indication for surgery, on the mortality and perhaps care unit patients and because E. coli, a common cause even on the development of multiorgan failure. How- of infected pancreatic necrosis, is rarely resistant to ever, infected necrosis and multiorgan failure are not necessarily parallel events in acute pancreatitis.43 In a third study, Delcenserie et al46 selected 23 patients with Sainio et al44 reported 60 patients with alcohol-induced alcohol-induced acute pancreatitis, whose CT scans necrotizing pancreatitis, proven by contrast-enhanced revealed two or more fluid collections within 48 hours, CT within 24 hours of admission. The mean Ranson following the onset of symptoms. They were randomly score was 5.5. Thus, according to this prognostic score, assigned to two groups: one receiving placebo treatment patients were more severely ill than those in the study by and one receiving antibiotics (ceftazidime, amikacin, and Pederzoli et al.42 Thirty patients were prescribed cefurox- metronidazole) for 10 days. Sepsis was diagnosed by ime (1.5 g intravenously three times a day until clinical positive blood cultures. Seven episodes of severe sepsis recovery and normalization of C-reactive protein [CRP] occurred (pancreatic infection and septic shock) in the concentrations). Thirty patients were assigned to control group, but no infections occurred in the antibiotic a control group. These patients did not receive any group (P , 0.03). Neither the incidence of multiple organ antibiotic treatment unless infection had been verified failure nor the mortality rate was significantly affected.
clinically, microbiologically, or radiologically or until The fourth study by Schwarz et al47 investigated 26 patients a second rise in CRP of more than 20%, after the acute with acute necrotizing pancreatitis, mostly of biliary phase. In cases where there was a full clinical recovery in origin and sterile pancreatic necrosis, as proven by the antibiotic group, with moderate CRP concentrations, contrast-enhanced CT and fine-needle aspiration. These antibiotic treatment was continued with oral cefuroxime patients were randomized into two groups: a control (250 mg/two times a day) for 14 days. Infectious comp- group (initially receiving no antibiotics) and a group lications were reduced from 1.8 in the control group to receiving intravenous ofloxacin (200 mg) and metroni- 1.0 in the antibiotic group (means, P = 0.01). When dazole (500 mg) twice a day. In both groups, fine-needle infectious complications were analyzed separately, only aspirations of the necrotic areas were performed on days urinary tract infections were significantly reduced in the 1, 3, 5, 7, and 10. When there was evidence of infection, treatment group. The most common cause of infections antibiotics were also given to the control patients. The was Staphylococcus epidermidis. This was also present extent of necrosis was identical (median, 40%) in both in the cultures taken from the necrotic pancreas, in 4 of groups. The necrotic tissue became infected within the 8 patients who had died of acute pancreatitis.
a median of 9.5 and 10 days (treatment and control Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Clin Gastroenterol  Volume 40, Number 2, February 2006 Antibiotic Prophylaxis in Acute Pancreatitis group). The clinical course, as documented by the for these subgroups were not given. However, 12% of the total APACHE-II score, should have significantly improved treatment group developed infected pancreatic necrosis com- under antibiotic treatment, but this neither prevented nor pared with 9% of the placebo group (difference not significant).
delayed bacterial infection of the necrotic pancreas.
Mortality was 5% in the treatment group and 7% in the placebo Within the first 3 weeks, 2 patients in the control group group. This is very low for necrotizing pancreatitis but not died but those in the treatment group survived (statistical surprising for a cohort in which the mean Ranson score on admission was between 2 and 3. To summarize, no differences Two meta-analyses of the available data indicated that pro- were observed in the rate of infected pancreatic necrosis, sys- phylactic antibiotics in patients with necrotizing pancre- atitis have a positive effect on the course of the disease.49,50This led to a number of recent guidelines and consensusdocuments recommending prophylactic antibiotic treat-ment of all patients with acute necrotizing pancreatitis.7–14 As most studies included only a limited number of patients, with none of them double-blinded or placebo-con- Whether the latest randomized trial suggests that anti- trolled, Isenmann et al51 performed a double-blinded, placebo- biotic treatment in general does not prevent infected pancreatic controlled study to investigate the effects of ciprofloxacin and necrosis, whether carbapenems are clearly superior to quino- metronidazole. This antibiotic combination had been shown to lones and metronidazole, or whether patients with mild pan- be effective in animal experiments.39 A total of 200 patients creatitis do not benefit from antibiotic treatment has to remain were chosen to demonstrate that antibiotic prophylaxis reduces an open question at this point. Recent studies suggest that the proportion of patients with infected pancreatic necrosis from imipenem and meropenem, although of equal effectiveness,52 40% in the placebo group to 20% in the ciprofloxacin and metronidazole group, with a power of 90%. After 50% of the There are two sides to this discussion. One group be- planned sample size was recruited, an adaptive interim analysis lieves that early treatment with carbapenems effectively pre- was performed and recruitment was stopped. A total of 114 pa- vents infected pancreatic necrosis and reduces mortality.42,53 tients were included in the intention-to-treat analysis. They The other believes that antibiotic treatment should be withheld had been selected by 19 participating hospitals over a period of unless the patient deteriorates.51 For the latter, criteria for 40 months, which indicates that each center contributed 6 cases initiating antibiotic treatment in patients with predicted severe over 3.5 years. Therefore, severe acute pancreatitis was a rare acute pancreatitis would be: the early development of sepsis or event at these centers. The criteria for predicted severe acute SIRS, the early failure of two or more organ systems, proven pancreatitis were serum CRP over 150 mg/L and/or necrosis on pancreatic or extrapancreatic infection, and an increase in CRP contrast-enhanced CT. Fifty-one (44.7%) patients were chosen, in combination with evidence of pancreatic or extrapancreatic on the basis of an elevated serum CRP in combination with pancreatic necrosis on CT. Nineteen (16.7%) patients had Routine use of broad-spectrum prophylactic antibiotics pancreatic necrosis on CT but a lower serum CRP, and 44 has altered the bacteriology of secondary pancreatic infection (38.5%) patients were chosen on the basis of an elevated serum in severe acute pancreatitis, from predominantly gram- CRP alone. In the latter group, 6 patients developed pancreatic negative coliforms to predominantly gram-positive organisms, necrosis during the subsequent course of the disease. Thus, without changing the rate of b-lactam resistance or fungal a total of 76 patients suffered from necrotizing pancreatitis. Of superinfection.54 It is unclear whether the use of long-term these, 41 patients were in the treatment group and 35 patients prophylactic antibiotic treatment, over longer periods, pro- were in the placebo group. A major end result of the study was motes fungal infection.55 Intraabdominal fungal infection was a reduction in infected pancreatic necrosis, either diagnosed by found in 37% of patients with severe acute pancreatitis and intraoperative smears by CT- or by ultrasound-guided fine- infected pancreatic necrosis.56 Pancreatic fungal infection was needle aspiration of those necrotic areas showing bacterial found in 24% of patients with proven necrotizing pancreatitis, infection. Other results included death, extrapancreatic infec- who had received prophylactic intravenous antibiotics.57 Early tion, surgical treatment of necrotizing pancreatitis, admission to treatment with fluconazole reduced fungal infections.56 the intensive care unit, hospitalization, and systemic compli- Whether broad-spectrum antibiotics in necrotizing pancreatitis cations of the disease, such as shock and pulmonary and renal should regularly be combined with antimycotic agents needs insufficiency. Treatment was planned to be given until day 21, after the onset of acute pancreatitis. When patients showedprogressive pancreatitis, characterized by clinical deteriorationand/or suspected pancreatic or extrapancreatic infection, anti-biotics were switched to open label treatment. In these cases, the TABLE 4. Criteria to Initiate Antibiotic Treatment in PatientsWith a Predicted Severe Course of Acute Pancreatitis51 use of imipenem, possibly in combination with vancomycin,was recommended. Twenty-eight percent in the treatment group Newly developed sepsis or systemic inflammatory response syndrome (SIRS) and 46% in the placebo group required open label antibiotic Newly developed failure of two or more organ systems treatment. About 96 different antibiotic regimes were given in Proven pancreatic or extrapancreatic infection the placebo group and 68 different regimes in the treatment Increase in serum C-reactive protein (CRP) in combination with evidence of pancreatic or extrapancreatic infection group. Thirty-one percent of these included a carbapenem. Data Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Clin Gastroenterol  Volume 40, Number 2, February 2006 TABLE 5. Antibiotic Decontamination of the Gut in Acute Experimental Pancreatitis (AEP) choline and supplemented with ethionine. Initially, after the Selective gut decontamination with oral nonresoluble administration of polymyxin B, amikacin, or amphotericin B, antibiotics is an alternative strategy, aimed at eliminating the survival rate did improve, but this did not continue. All pathogens in the intestinal flora and reducing bacterial antibiotics used, reduced the number of bacteria in the cecum, translocation. This would reduce the risk of pancreatic infection but only some reduced the rate of translocation of gram- (Table 5).58 This approach was tested almost 50 years ago by positive and gram-negative microorganisms to all organs.
Persky et al,59 who induced acute pancreatitis in dogs by The only controlled clinical study of selective de- injecting bile into the pancreatic duct. The mortality rate for this contamination was performed by Luiten et al63 in a multicenter experimental pancreatitis was higher than 90%. Aureomycin, trial. This involved 102 patients who had severe acute given orally for 5 to 10 days, until coliform microorganisms pancreatitis. Patients were randomly assigned to a standard were absent in the feces on 3 consecutive days, reduced the treatment group or to a group receiving standard treatment mortality rate to zero. In another experiment, Aureomycin was plus selective decontamination drugs. These consisted of an given immediately after the operation; but because many oral administration of colistin sulfate, amphotericin B, and capsules had not dissolved, the mortality rate was 75%. When norfloxacin given every 6 hours. In addition, a rectal enema Aureomycin was suspended in water and given by gavage was given every day. This contained the same three antibio- immediately after the operation, the mortality rate was again tics, at the same concentration as the oral administration.
zero. In contrast, Aureomycin given intravenously, immediately This regimen was supplemented by systemic treatment with postoperatively, resulted in a survival rate of 40%.59 cefotaxime, which was given every 8 hours until gram- These early animal experiments showed for the first time negative microorganisms were eliminated from the oral cavity that gut decontamination is beneficial in acute experimental and rectum. The mortality rate was 35% in the control group pancreatitis. These were forgotten for many decades until and 22% in the group given selective decontamination (P = Lange et al60 induced acute experimental pancreatitis in the 0.048). This difference was mainly caused by a reduction in rat, to study the effect of gut decontamination again. Rats the late mortality (.2 weeks) because of a significant re- underwent either a subtotal colectomy or intestinal lavage plus duction of gram-negative pancreatic infection (P = 0.003).
an infusion of kanamycin. Both procedures had a significant Furthermore, in the group who were receiving selective de- beneficial effect on the mortality rate, thus indicating that the contamination, the average number of laparotomies per patient intestinal flora was a major factor affecting mortality in this Because this treatment combines selective gut de- Isaji et al61 studied the effect of bacterial infection in mice contamination with systemic antibiotic treatment, it is difficult with diet-induced acute pancreatitis. Oral application of to conclude which of the treatment components accounted for bacitracin, metronidazole, and neomycin increased the survival rate significantly and tended to slightly reduce infection.
Foitzik et al38 studied different strategies of antibiotic treatment of the prevention of early pancreatic infection in an experimental model. Acute pancreatitis was induced by 1. Beger HG, Bittner R, Block S, et al. Bacterial contamination of pancreatic a combination of an intraductal injection of glycodeoxycholic necrosis: a prospective clinical study. Gastroenterology. 1986;91:433–438.
2. Lankisch PG, Banks PA. Pancreatitis. Berlin: Springer, 1998.
acid in addition to intravenous cerulein hyperstimulation of the 3. Banks PA, Gerzof SG, Langevin RE, et al. CT-guided aspiration of gland. Treatment was begun 6 hours after the induction of suspected pancreatic infection: bacteriology and clinical outcome. Int J acute pancreatitis. Mortality was unaffected by any treatment regimen, but pancreatic infection was significantly reduced 4. Hiatt JR, Fink AS, King W III, et al. Percutaneous aspiration of with full gut decontamination and with imipenem. It was not peripancreatic fluid collections: a safe method to detect infection. Surgery.
1987;101:523–530.
improved with oral antibiotics or with cefotaxime alone.
5. Evans WK, Ho C-S, McLoughlin MJ, et al. Fatal necrotizing pancreatitis Gianotti et al62 studied various antibiotics in mice, in following fine-needle aspiration biopsy of the pancreas. Radiology. 1981; which acute pancreatitis was induced by a diet deficient in Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Clin Gastroenterol  Volume 40, Number 2, February 2006 Antibiotic Prophylaxis in Acute Pancreatitis 6. Levin DP, Bret PM. Percutaneous fine-needle aspiration biopsy of the 37. Araida T, Frey CF, Ruebner B, et al. Therapeutic regimens in acute exper- pancreas resulting in death. Gastrointest Radiol. 1991;16:67–69.
imental pancreatitis in rats: effects of a protease inhibitor, a b-agonist, 7. Bradley EL III. A clinically based classification system for acute pancreatitis: and antibiotics. Pancreas. 1995;11:132–140.
summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, 38. Foitzik T, Ferna´ndez-del Castillo C, Ferraro MJ, et al. Pathogenesis and September 11 through 13, 1992. Arch Surg. 1993;128:586–590.
prevention of early pancreatic infection in experimental acute necrotizing 8. Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objective assessment pancreatitis. Ann Surg. 1995;222:179–185.
of severity, and management of acute pancreatitis. Int J Pancreatol. 1999; 39. Mitho¨fer K, Ferna´ndez-del Castillo C, Ferraro MJ, et al. Antibiotic treat- ment improves survival in experimental acute necrotizing pancreatitis.
9. Ru¨nzi M, Layer P, Bu¨chler MW, et al. Therapie der akuten Pankreatitis.
Gastroenterology. 1996;110:232–240.
Gemeinsame Leitlinien. Z Gastroenterol. 2000;38:571–581.
40. Trudel JL, Wittnich C, Brown RA. Antibiotics bioavailability in acute 10. Toouli J, Brooke-Smith M, Bassi C, et al. Working party report: guidelines experimental pancreatitis. J Am Coll Surg. 1994;178:475–479.
for the management of acute pancreatitis. J Gastroenterol Hepatol. 2002; 41. Barie PS. A critical review of antibiotic prophylaxis in severe acute pancreatitis. Am J Surg. 1996;172(suppl 6A):38–43.
11. Mayumi T, Ura H, Arata S, et al. Evidence-based clinical practice guide- 42. Pederzoli P, Bassi C, Vesentini S, et al. A randomized multicenter lines for acute pancreatitis: proposals. J Hepatobiliary Pancreat Surg.
clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet. 1993;176: 12. Uhl W, Warshaw A, Imrie C, et al. IAP guidelines for the surgical management of acute pancreatitis. Pancreatology. 2002;2:565–573.
43. Tenner S, Sica G, Hughes M, et al. Relationship of necrosis to organ 13. Glazer G, Mann DV. United Kingdom guidelines for the management of failure in severe acute pancreatitis. Gastroenterology. 1997;113:899–903.
acute pancreatitis. Gut. 1998;42(suppl 2):1–13.
44. Sainio V, Kemppainen E, Puolakkainen P, et al. Early antibiotic treatment 14. SSAT. SSAT patient care guidelines: treatment of acute pancreatitis.
in acute necrotising pancreatitis. Lancet. 1995;346:663–667.
J Gastrointest Surg. 1998;2:487–488.
45. Baudin F, Ozier Y. Early antibiotic treatment in acute necrotising 15. Lankisch PG, Weber-Dany B, Lerch MM. Diagnose und Therapie der pancreatitis. Lancet. 1995;346:1374–1376.
akuten Pankreatitis: Werden die Leitlinien akzeptiert? Dtsch Med 46. Delcenserie R, Yzet T, Ducroix JP. Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis. Pancreas. 1996;13:198–201.
16. Lankisch PG, Weber-Dany B, Lerch MM. Clinical perspectives in 47. Schwarz M, Isenmann R, Meyer H, et al. Antibiotika bei nekrotisierender pancreatology: compliance with acute pancreatitis guidelines in Germany.
Pankreatitis. Ergebnisse einer kontrollierten Studie. Dtsch Med Wo- 17. Dubner H, Steinberg W, Hill M, et al. Infected pancreatic necrosis and 48. Nordback I, Sand J, Saaristo J, et al. Early treatment with antibiotics peripancreatic fluid collections: serendipitous response to antibiotics and reduces the need for surgery in acute necrotizing pancreatitis: a single- medical therapy in three patients. Pancreas. 1996;12:298–302.
center randomized study. J Gastrointest Surg. 2001;5:113–120.
18. Adler DG, Chari ST, Dahl TJ, et al. Conservative management of infected 49. Golub R, Siddiqi F, Pohl D. Role of antibiotics in acute pancreatitis: necrosis complicating severe acute pancreatitis. Am J Gastroenterol.
a meta-analysis. J Gastrointest Surg. 1998;2:496–503.
50. Sharma VK, Howden CW. Prophylactic antibiotic administration reduces 19. Runzi M, Niebel W, Goebell H, et al. Severe acute pancreatitis: sepsis and mortality in acute necrotizing pancreatitis: a meta-analysis.
nonsurgical treatment of infected necroses. Pancreas. 2005;30:195–199.
20. Pederzoli P, Orcalli F, Falconi M, et al. Penetration of mezlocillin into 51. Isenmann R, Ru¨nzi M, Kron M, et al. Prophylactic antibiotic treatment in pancreatic juice. J Antimicrob Chemother. 1986;17:397.
patients with predicted severe acute pancreatitis: a placebo-controlled, 21. Roberts EA, Williams RJ. Ampicillin concentrations in pancreatic fluid double-blind trial. Gastroenterology. 2004;126:997–1004.
bile obtained at endoscopic retrograde cholangiopancreatography 52. Manes G, Rabitti PG, Menchise A, et al. Prophylaxis with meropenem of (ERCP). Scand J Gastroenterol. 1979;14:669–672.
septic complications in acute pancreatitis: a randomized, controlled trial 22. Koch K, Drewelow B, Liebe S, et al. Die Pankreasga¨ngigkeit von versus imipenem. Pancreas. 2003;17:e79–e83.
Antibiotica. Chirurg. 1991;62:317–322.
53. Bassi C, Falconi M, Talamini G, et al. Controlled clinical trial of 23. Brattstro¨m C, Malmborg A-S, Tyde´n G. Penetration of clindamycin, pefloxacin versus imipenem in severe acute pancreatitis. Gastroenterology.
cefoxitin, and piperacillin into pancreatic juice in man. Surgery. 1988;103: 54. Howard TJ, Temple MB. Prophylactic antibiotics alter the bacteriology 24. Gregg JA, Maher L, DeGirolami PC, et al. Secretion of b-lactam of infected necrosis in severe acute pancreatitis. J Am Coll Surg. 2002; antibiotics in pure human pancreatic juice. Am J Surg. 1985;150:333–335.
25. Pederzoli P, Falconi M, Bassi C, et al. Ofloxacin penetration into bile and 55. Gloor B, Schmidt O, Uhl W, et al. Acute pancreatitis: threat of fungal pancreatic juice. J Antimicrob Chemother. 1989;23:805–807.
infection. Pancreatology. 2001;1:213–216.
26. Pederzoli P, Falconi M, Bassi C, et al. Ciprofloxacin penetration in 56. De Waele JJ, Vogelaers D, Blot S, et al. Fungal infections in patients with pancreatic juice. Chemotherapy. 1987;33:397–401.
severe acute pancreatitis and the use of prophylactic therapy. Clin Infect 27. Bassi C, Pederzoli P, Vesentini S, et al. Behavior of antibiotics during human necrotizing pancreatitis. Antimicrob Agents Chemother. 1994;38:830–836.
57. Gloor B, Mu¨ller CA, Worni M, et al. Pancreatic infection in severe 28. Drewelow B, Koch K, Otto C, et al. Penetration of ceftazidime into human pancreatitis: the role of fungus and multiresistant organisms. Arch Surg.
pancreas. Infection. 1993;21:229–234.
29. Bu¨chler M, Malfertheiner P, Frieß H, et al. Human pancreatic tissue concen- 58. Powell JJ, Miles R, Siriwardena AK. Antibiotic prophylaxis in the ini- tration of bactericidal antibiotics. Gastroenterology. 1992;103:1902–1908.
tial management of severe acute pancreatitis. Br J Surg. 1998;85:582– 30. Koch K, Drewelow B, Brinckmann W. Die Pankreaspenetration von Ofloxacin: Eine Pilotstudie. Z Gastroenterol. 1993;31:587–591.
59. Persky L, Schweinburg FB, Jacob S, et al. Aureomycin in experimental 31. Lankisch PG, Klesel N, Seeger K, et al. Penetration of cefotaxime into the acute pancreatitis of dogs. Surgery. 1951;30:652–656.
pancreas. Z Gastroenterol. 1983;21:601–603.
60. Lange JF, van Gool J, Tytgat GNJ. The protective effect of a reduction in 32. Benveniste GL, Morris RG. Penetration of cefotaxime into pancreatic intestinal flora on mortality of acute haemorrhagic pancreatitis in the rat.
Hepatogastroenterology. 1987;34:28–30.
33. Craig RM, Dordal E, Myles L. The use of ampicillin in acute pancreatitis.
61. Isaji S, Suzuki M, Frey CF, et al. Role of bacterial infection in diet-induced acute pancreatitis in mice. Int J Pancreatol. 1992;11:49–57.
34. Finch WT, Sawyers JL, Schenker S. A prospective study to determine 62. Gianotti L, Munda R, Gennari R, et al. Effect of different regimens of gut the efficacy of antibiotics in acute pancreatitis. Ann Surg. 1976;183:667–671.
decontamination on bacterial translocation and mortality in experimental 35. Howes R, Zuidema GD, Cameron JL. Evaluation of prophylactic acute pancreatitis. Eur J Surg. 1995;161:85–92.
antibiotics in acute pancreatitis. J Surg Res. 1975;18:197–200.
63. Luiten EJT, Hop WCJ, Lange JF, et al. Controlled clinical trial of selective 36. Widdison AL, Karanjia ND, Reber HA. Antimicrobial treatment of decontamination for the treatment of severe acute pancreatitis. Ann Surg.
pancreatic infection in cats. Br J Surg. 1994;81:886–889.
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